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Supratentorial overlay definition betting

Outlasting modulatory effects in the sensorimotor cortex have been observed following sustained electrical Chipchase et al. Peripheral pressure stimulation has been studied less extensively Miura et al. The technique, also known as Vojta method, uses sustained manual pressure stimulation of specific body surface areas to gradually evoke a stereotypic pattern of tonic muscle contractions in both sides of the neck, trunk, and limbs Vojta, It has been speculated that the motor response is controlled by a brainstem region Laufens et al.

Indeed, we have previously shown that heel stimulation according to Vojta specifically modulates subsequent motor task-related activation in the dorsal pons, medulla presumably in the pontomedullary reticular formation, PMRF , and cerebellum Hok et al. Nevertheless, there is limited knowledge of the immediate neurobiological correlates of the therapeutic stimulation and the resulting interaction between the somatosensory and motor system. Previous imaging studies of pressure stimulation recently provided valuable, yet still incomplete picture of the central somatosensory processing Hao et al.

Miura et al. Similar pattern has been observed during 30 s of 1-Hz sinusoidal pressure applied to the foot sole Hao et al. Chung et al. Only one study assessed cortical activation during manual stimulation according to Vojta applied to an active site at the anterior thorax Sanz-Esteban et al. However, methodological issues, such as unbalanced group sizes, a control site in a distant body part, and statistical maps uncorrected for multiple comparisons, do not permit drawing strong conclusions Sanz-Esteban et al.

To our knowledge, no previous imaging study evaluated immediate central effects of pressure stimulation of the foot according to reflex locomotion therapy Vojta, ; Vojta and Peters, , and in general, there are no fMRI data on responses to pressure foot stimulation delivered continuously over at least 30 s.

In summary, it is unknown whether the sensorimotor system response is influenced by a specific stimulation site, e. Furthermore, the link between the previously reported modulation of the motor task-evoked activation Hok et al. We hypothesized that, first, different body sites would differentially influence sensorimotor system during the stimulation, and second, that a site used in the reflex locomotion therapy would specifically activate the PMRF Hok et al.

To address these hypotheses, we employed fMRI during block-designed sustained pressure stimulation at either an active Vojta, or control site on the foot. We expected to identify the general activation pattern of cortical and subcortical areas involved in the central processing of sustained pressure stimulation of the foot while simulating clinical conditions of manual physiotherapy.

However, analysis of fMRI responses to sustained pressure stimulation has to address two physiological challenges: First, cortical response adapts rapidly within somatosensory areas, where it decreases exponentially over several seconds Chung et al. Second, the activation of the presumed generators of the gradually developing widespread tonic motor reflex response would be expected to follow the same slow timecourse supposedly resulting from temporal summation over tens of seconds Vojta, Both phenomena preclude the use of common models convolving a rectangular stimulus function with the canonical HRF.

Therefore, we utilized a more flexible modeling approach, namely, a convolution with a set of FIR basis functions. The main hypotheses were tested quantitatively on a voxel-wise basis, evaluating within-subject differences between the active and control stimulation. Nevertheless, the FIR model does not assume any specific shape of the hemodynamic response, which may differ slightly among different brain areas and even within one functional system Glover, ; Lewis et al.

Since there is no common reference for the BOLD signal throughout the brain, interpretation of significant differences critically relies on identification of brain areas that significantly respond to the stimulation and the timecourse of these evoked responses. Therefore, on top of the paired analysis of stimulus-related differences, we have employed a correlation-based clustering approach to characterize the shape of group-wise BOLD responses at different levels of the sensorimotor system and to delineate subsystems that differentially respond to the stimulation and may have different functions.

Materials and Methods Study Design This proof-of-concept study has been conducted as a randomized cross-over experimental study in a single cohort of healthy adults to determine the central effects of the sustained manual pressure stimulation according to Vojta reflex locomotion Vojta, ; Vojta and Peters, versus a sham stimulation.

Participants Thirty healthy volunteers enrolled in this study 16 females and 14 males, mean age Twenty-seven subjects were right-handed and three were left-handed according to the Edinburgh handedness inventory Oldfield, Task and Procedures Each fMRI session included 2 functional imaging acquisitions during 10 min of right foot stimulation.

Prior to the stimulation, participants performed a sequential motor task with their right hand as described elsewhere Hok et al. During the stimulation, participants were lying prone in the scanner bore with their eyes closed and were asked not to think about anything in particular. The stimulation was delivered in twelve blocks each 30 s long alternating with jittered rest to permit modeling of the extended hemodynamic response Dale, In total, this resulted in 6 min of stimulation and 4 min of rest per acquisition run.

The therapists were instructed to apply manual pressure similar to that routinely used during physiotherapy according to Vojta. However, the use of a single stimulation site, the specific body position and stimulation duration, were chosen to elicit only partial motor response Vojta and Peters, , avoiding gross body movements and head displacement in the scanner bore.

The session order was randomized and counter-balanced, and the participants were not informed in advance that the stimulation would be performed in one of two different sites. The posterior lesion shows no signs of blood-brain barrier disruption, an increased average tissue sodium signal and a reduced fluid-attenuated sodium signal — a combination consistent with the residuals of brain tissue inflammation white arrowhead.

Full size image Multiple sclerosis lesions MS lesion volumes of interest were defined by T2-FLAIR signal alterations and, where applicable, by the T1 signal of contrast-enhancing portions. Thereby, the presence acute lesion or absence of contrast enhancement chronic lesion determined the type of lesion. Lesions less than 30 mm2 in volume, and less than 5 mm in transversal diameter were discarded from further analysis to reduce partial volume effects.

All included lesions were located within white matter. Outlier corrections removed data diverging by 2. Plausibility checks controlled for T1 CE signals to be higher in acute compared to chronic lesions; lesions not fulfilling these criteria were removed from further analysis. Statistical analysis Prediction of lesion type For each lesion its type acute vs. The predictive value of average tissue sodium signal and fluid-attenuated sodium signal was explored by adding these predictors successively to a base model and evaluating whether these led to an improvement of the model which outweighed the additional number of free parameters using likelihood ratio tests.

Several other factors possibly associated with lesion type were controlled for by adding them as predictors to all models. In detail, age, gender, methylprednisolone application, medication other than methylprednisolone, expanded disability status scale EDSS score, and disease duration were included in all models.

Model parameters were estimated using Laplace approximation as implemented in the lme4 package 30 in R. To ease convergence of the algorithm all continuous predictors were scaled, i. Correlation analyses As for the prediction of lesion type a hierarchical design was used to test for the relationship between sodium and proton MRI signals, thereby, controlling for differences in the number of lesion types across participants.

Note that due to the hierarchical design fixed effects parameters are free of inter-subject variability in the strength of the signal, thus, being higher than suggested from a scatterplot across all data points. Therefore, scatterplots are not shown here. Statistical significance of the estimated parameter values was tested using type III Wald chi-square tests.

Longitudinal data This analysis aimed at revealing changes in sodium MRI signals after steroid therapy. To this aim, average tissue and fluid-attenuated sodium signals were separately predicted by the timepoint of signal measurement. This analysis compares signal values between pre- and post-medication states while accounting for differences in lesion number and average signal strength in single patients.

A statistical model based on data from three patients cannot be representative with regard to the whole patient group. To derive a measure of confidence for parameter estimates from this model we performed , parametric bootstraps of each model. Outlier corrections and plausibility checks cf. The average, as well as the fluid-attenuated sodium signal of acute MS lesions were thus significantly elevated compared to chronic MS lesions.

In Fig. Intra-individual A; PID no. Similar, inter-individual B; PIDs no. In acute lesions the intra- and inter-individual average tissue and the fluid-attenuated sodium signals are increased compared to chronic lesions. Scatter plots and histograms of both sodium signals visualize intra- and inter-individual examples with ideal separation of acute and chronic lesions by average tissue and fluid-attenuated sodium signals; this is not true for all lesions, that is, scatter plots of MS lesions can be larger, and may be somewhat overlapping between lesion types.

This may be, at least in part, owed to the fact that both, T2 signal and contrast enhancement are primarily unspecific 14 , Nevertheless, generalized linear mixed models revealed a significant improvement of lesion type classification by the average as well as the fluid-attenuated sodium signal. Both signals were significantly increased in acute lesions. There was no correlation between average tissue sodium signal and T1 CE signal.

Of note, there was no correlation between average tissue and fluid-attenuated sodium signals. Longitudinal experiment Hierarchical comparisons of average tissue and fluid-attenuated sodium signals across pre- and post-medication measurements revealed a decrease of both signals after the application of high-dose methylprednisolone. Average tissue sodium signals decreased by estimated 0. Fluid-attenuated sodium signals even decreased by 1. Longitudinal sodium MRI data are shown in Figs 3 and 4. After application of high-dose methylprednisolone both the average tissue and fluid-attenuated sodium signal decrease.

Based upon the cross sectional findings on sodium signal differences between acute and chronic MS lesions, this signal behavior was proposed before. Moreover, it strongly supports the notion that findings of our study are compatible with intracellular sodium accumulation in acute inflammatory MS lesions. Please note, that due to the pharmacological intervention changes in tissue sodium concentration of healthy parenchyma could not be ruled out.

Thus, for the longitudinal observations, normalization referred to transmitter amplitudes instead of the sodium signal of healthy parenchyma. Sodium signal changes after administration of high-dose methylprednisolone support findings of the cross-sectional analyses. Hierarchical comparisons of average tissue and fluid-attenuated sodium signals across pre- and post-medication measurements revealed a decrease of both signals after the application of high-dose methylprednisolone cf.

Methods and Results section for details. Full size image Discussion Our study confirms that both, the average tissue sodium signal and the fluid-attenuated sodium signal significantly differ between acute and chronic MS lesions of human brain parenchyma. Additional longitudinal sodium data from before and after application of high-dose methyprednisolone demonstrate that these differences are MS specific. Therefore, the detected increase in fluid-attenuated sodium signal is compatible with the intracellular sodium accumulation observed in acute MS lesions.

This finding is in excellent agreement with previous reports on increased expression of sodium channels, and intracellular sodium accumulation occurring as pathophysiological event in experimental autoimmune encephalomyelitis EAE and MS 11 , 12 , Moreover, consistent with results of our study, Petracca and colleagues 32 demonstrated sodium signals at a brain regional level that might reflect neuro-axonal metabolic dysfunction in MS.

There is strong evidence that sodium channels play an important role in immune cell function in EAE and MS 11 , In MS lesions, activated microglia and infiltrated macrophages 4 produce reactive-oxygen species and nitric oxide 3 , which impair mitochondrial function in neurons 37 , Thereby, ATP production and energy supply is reduced.

Concurrently, there is an increased neuronal energy demand due to the redistribution, as well as the co-localization of Nav1. This mismatch between energy supply and demand thereby creates a state of virtual hypoxia 39 , and leads to an accumulation of intracellular sodium ions 12 similar to the pathogenic cascade following ischemic stroke

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The truth is clear-cut overlays surface about as often as the Cleveland Browns make the NFL playoffs sorry Browns fans. Not only that, but determining what an overlay actually is can be equally confounding. Should the nondescript first-time starter with so-so works be or ? Naturally, Joe lost the wager when the dealer produced paperwork proving the car in question was, indeed, a Charger.

Secondly, by eliminating severe underlays in a race, one naturally creates a positive betting scenario, whereby dutching some or all of the remaining contenders becomes a viable wagering option. Thus, determining the fair odds on the aforementioned first-time starter becomes a moot point. OK, I hear some of you saying, so how does one go about ferreting out false favorites? I have two primary recommendations: Analyze trainer intentions, which is particularly effective in cheaper claiming races.

Look for heavily bet favorites with just a few lifetime starts.